Enabling Suzuki–Miyaura coupling of Lewis-basic arylboronic esters with a nonprecious metal catalyst

Haibach, Michael C.; Ickes, Andrew R.; Tcyrulnikov, Sergei; Shekhar, Shashank; Monfette, Sébastien; Swiatowiec, Rafal; Kotecki, Brian J.; Wang, Jason; Wall, Amanda L; Henry, Rodger F.; Hansen, Eric C.

doi:10.1039/d2sc03877c

Cited by 10 publications

(8 citation statements)

References 58 publications

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“…We evaluated the performance of ProPhos in Ni-SMC with respect to its compatibility with heterocycles, which are typically challenging substrates (Scheme ). , Without extensive catalyst optimization, we employed a mixed solvent system consisting of 2-MeTHF/H 2 O for ArBPin and i PrOH for ArB(OH) 2 . Notably, NiCl 2 ·6H 2 O proved to be effective in i PrOH with a range of boronic acids, yielding the desired products.…”

Section: Resultsmentioning

confidence: 99%

“…Recent efforts aimed at improving Ni-SMC have revealed that a monodentate phosphine ligand can facilitate oxidative addition and transmetalation, while a bidentate phosphine ligand can stabilize the catalyst against deactivation . This insight resonates with the recent application of Ph 2 MeP, Buchwald-type ligands, and dppb (dppb = 1,4-bis(diphenylphosphino)butane) in Ni-SMC. While data analysis and machine learning models emerge as powerful tools for identifying new ligands, a complementary strategy involves design based on mechanistic understanding.…”

Section: Introductionmentioning

confidence: 83%

“…Diphenylmethylphosphine (Ph 2 MeP) is currently recognized as one of the most effective catalysts in Ni-SMC. 16 To develop a scaffolding ligand, we synthesized a series of ligands featuring hydroxyl, ester, and silyl ether groups tethered to diphenylphosphine through linkages of various lengths (Figure 1A). Our studies began with testing these ligands in a model SMC of 4 and 5 to afford 7 using a catalyst loading of 0.5 mol % at 60 °C.…”

Section: ■ Introductionmentioning

confidence: 99%

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ProPhos: A Ligand for Promoting Nickel-Catalyzed Suzuki-Miyaura Coupling Inspired by Mechanistic Insights into Transmetalation

Yang,

Neary,

Diao

2024

J. Am. Chem. Soc.

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Nickel-catalyzed Suzuki−Miyaura coupling (Ni-SMC) offers the potential to reduce the cost of pharmaceutical process synthesis. However, its application has been restricted by challenges such as slow reaction rates, high catalyst loading, and a limited scope of heterocycles. Despite recent investigations, the mechanism of transmetalation in Ni-SMC, often viewed as the turnover-limiting step, remains insufficiently understood. We elucidate the "Ni-oxo" transmetalation pathway, applying PPh 2 Me as the ligand, and identify the formation of a nickel-oxo intermediate as the turnover-limiting step. Building on this insight, we develop a scaffolding ligand, ProPhos, featuring a pendant hydroxyl group connected to the phosphine via a linker. The design preorganizes both the nucleophile and the nickel catalyst, thereby facilitating transmetalation. This catalyst exhibits fast kinetics and robust activity across a wide range of heteroarenes, with a catalyst loading of 0.5−3 mol %. For arene substrates, the catalyst loading can be further reduced to 0.1 mol %.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 83%

Section: ■ Introductionmentioning

confidence: 99%

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ProPhos: A Ligand for Promoting Nickel-Catalyzed Suzuki-Miyaura Coupling Inspired by Mechanistic Insights into Transmetalation

Yang,

Neary,

Diao

2024

J. Am. Chem. Soc.

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“…Notably, a common limitation of nearly all prior art was the use of inorganic bases with poor solubility in organic solvents, such as K 3 PO 4 and K 2 CO 3 , often in conjunction with small yet highly specific amounts of water that is either intentionally added or adventitiously present in the inorganic base. , From the standpoint of reproducibility, robustness and scalability, each of these features were significant drawbacks that we sought to overcome. We considered that the ideal solution would involve the identification of a modular, air-stable precatalyst that readily undergoes activation and promotes cross-coupling at low catalyst loadings using a soluble base with tolerance for a wide range of water levels (Figure ).…”

Section: Earth-abundant Metals As Replacements For Palladiummentioning

confidence: 99%

“…While Pd-catalyzed SMCs commonly employ water as a cosolvent, such conditions are rare for nickel. , A potential explanation for this is suggested by the elegant mechanistic studies performed by Grimaud and co-workers, which point to the facile formation of off-cycle Ni μ-hydroxo dimer species that do not readily undergo transmetalation with organoboron nucleophiles . We hypothesized that a weak amine base might enable more robust water-tolerant conditions by minimizing the amount of Ni hydroxide species present in the reaction mixture.…”

Section: Earth-abundant Metals As Replacements For Palladiummentioning

confidence: 99%

Collaboration as a Key to Advance Capabilities for Earth-Abundant Metal Catalysis

Chirik

Engle

Simmons

et al. 2023

Org. Process Res. Dev.

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Earth-abundant metal (EAM) catalysis can have profound impact in the pharmaceutical industry in terms of sustainability and cost improvements from replacing precious metals like palladium as well as harnessing the differential reactivity of first-row metals that allows for novel transformations to enable more efficient routes to clinical candidates. The strategy for building these capabilities within the process group at Bristol Myers Squibb is described herein, with the general plan of building a reaction screening platform, demonstrating scalability, and increasing mechanistic understanding of the reaction and catalyst activation. The development of catalytic transformations utilizing nickel, cobalt, and iron is described while highlighting the importance of collaboration with internal and external groups to advance EAM catalysis and impact our portfolio. The challenges and benefits of working with first-row transition metals, including metrics for the implementation of EAM catalysis, such as cost, process mass intensity, and commercial availability of catalysts and ligands, are discussed.

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Electroreductive Synthesis of Nickel(0) Complexes**

Rubel,

Cao,

El‐Hayek Ewing

et al. 2023

Angewandte Chemie

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Over the last fifty years, the use of nickel catalysts for facilitating organic transformations has skyrocketed. Nickel(0) sources act as useful precatalysts because they can enter a catalytic cycle through ligand exchange, without needing to undergo additional elementary steps. However, most Ni(0) precatalysts are synthesized with stoichiometric aluminum–hydride reductants, pyrophoric reagents that are not atom‐economical and must be used at cryogenic temperatures. Here, we demonstrate that Ni(II) salts can be reduced on preparative scale using electrolysis to yield a variety of Ni(0) and Ni(II) complexes that are widely used as precatalysts in organic synthesis, including bis(1,5‐cyclooctadiene)nickel(0) [Ni(COD)2]. This method overcomes the reproducibility issues of previously reported methods by standardizing the procedure, such that it can be performed anywhere in a robust manner. It can be transitioned to large scale through an electrochemical recirculating flow process and extended to an in situ reduction protocol to generate catalytic amounts of Ni(0) for organic transformations. We anticipate that this work will accelerate adoption of preparative electrochemistry for the synthesis of low‐valent organometallic complexes in academia and industry.

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Enabling Suzuki–Miyaura coupling of Lewis-basic arylboronic esters with a nonprecious metal catalyst

Abstract: The high cost and negative environmental impact of precious metal catalysts has led to increased demand for nonprecious alternatives for widely practiced reactions such as the Suzuki-Miyaura coupling (SMC). Ni-catalyzed...

Cited by 10 publications

References 58 publications

ProPhos: A Ligand for Promoting Nickel-Catalyzed Suzuki-Miyaura Coupling Inspired by Mechanistic Insights into Transmetalation

ProPhos: A Ligand for Promoting Nickel-Catalyzed Suzuki-Miyaura Coupling Inspired by Mechanistic Insights into Transmetalation

Collaboration as a Key to Advance Capabilities for Earth-Abundant Metal Catalysis

Electroreductive Synthesis of Nickel(0) Complexes**

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